title: ABT-335, the choline salt of fenofibric acid, does not have a clinically significant pharmacokinetic interaction with rosuvastatin in humans.
abstract: ABT-335 is the choline salt of fenofibric acid under clinical development as a combination therapy with rosuvastatin for the management of dyslipidemia. ABT-335 and rosuvastatin have different mechanisms of actions and exert complementary pharmacodynamic effects on lipids. The current study assessed the pharmacokinetic interaction between the 2 drugs following a multiple-dose, open-label, 3-period, randomized, crossover design. Eighteen healthy men and women received 40 mg rosuvastatin alone, 135 mg ABT-335 alone, and the 2 drugs in combination once daily for 10 days. Blood samples were collected prior to dosing on multiple days and up to 120 hours after day 10 dosing for the measurements of fenofibric acid and rosuvastatin plasma concentrations. Coadministering 40 mg rosuvastatin had no significant effect on the steady-state Cmax, Cmin, or AUC24 of fenofibric acid (P > .05). Coadministering ABT-335 had no significant effect on the steady-state Cmin or AUC24 of rosuvastatin (P > .05) but increased Cmax by 20% (90% confidence interval: 12%-28%). All 3 regimens were generally well tolerated with no clinically significant changes in clinical laboratory values, vital signs, or electrocardiograms during the study. Results from this study demonstrate no clinically significant pharmacokinetic interaction between ABT-335 at the full clinical dose and rosuvastatin at the highest approved dose.
authors.affiliation: Abbott, Abbott Park, IL 60064-6104, USA. Tong.Zhu@abbott.com
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.forename: Walid M
authors.initials: WM
authors.lastname: Awni
authors.forename: Balakrishna
authors.initials: B
authors.lastname: Hosmane
authors.forename: Maureen T
authors.initials: MT
authors.lastname: Kelly
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Sleep
authors.forename: James C
authors.initials: JC
authors.lastname: Stolzenbach
authors.forename: Katty
authors.initials: K
authors.lastname: Wan
authors.forename: Titus O
authors.initials: TO
authors.lastname: Chira
authors.forename: Rajendra S
authors.initials: RS
authors.lastname: Pradhan
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005464:Fluorobenzenes / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: C533234:2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoic acid; D005464:Fluorobenzenes; D000960:Hypolipidemic Agents; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; C006012:fenofibric acid; D011345:Fenofibrate